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A cholinergic mechanism orchestrating task-dependent computation across the cortex
Biorxiv : the Preprint Server for Biology
|December 15, 2025
Summary
Acetylcholine release in the cortex orchestrates brain activity for specific tasks. This neuromodulator is crucial for evidence accumulation during decision-making, highlighting its role in cognitive flexibility.
Area of Science:
- Neuroscience
- Cognitive Science
- Cholinergic Systems
Background:
- Animals must adapt cognitive processes for different tasks in dynamic environments.
- Cortical neural activity dynamics are influenced by task demands and behavioral strategies.
- The circuit mechanisms orchestrating task-dependent cortical dynamics remain largely unknown.
Purpose of the Study:
- To investigate the role of acetylcholine release in the cortex in orchestrating task-dependent neural dynamics.
- To test the hypothesis that the basal forebrain cholinergic system is key to cognitive flexibility.
- To elucidate the function of cholinergic input in evidence accumulation during decision-making.
Main Methods:
- Imaged cholinergic axons in the cortex of mice performing distinct virtual reality decision-making tasks.
- Analyzed spatiotemporal patterns of cholinergic activity in relation to task demands and strategy.
- Used optogenetics to silence cholinergic terminals and assess causal effects on cortical activity and behavior.
Main Results:
- Cholinergic input to the cortex is heterogeneous, multiplexing various signals in a task-dependent manner.
- Cholinergic activity specifically encoded an evidence-dependent decision variable during evidence accumulation.
- Silencing cholinergic terminals selectively impaired evidence accumulation and cortical coding during this task.
Conclusions:
- Identified a novel cholinergic mechanism orchestrating cortex-wide activity for task-specific computations.
- Cholinergic system plays a causal role in evidence accumulation and decision-making processes.
- Cholinergic input is a key node in brain networks supporting cognitive flexibility and sensory evidence integration.
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